The main objectives of our proposed hemoglobin research are: (1) to understand the molecular mechanism for the cooperative oxygenation of human adult hemoglobin and (2) to correlate the structure-function relationships in human abnormal hemoglobins found in hemoglobinopathies. Our basic experimental approach is to apply physical-chemical techniques, in particular nuclear magnetic resonance (NMR) spectroscopy, to pinpoint spectral differences among hemoglobins. By choosing appropriate human mutant hemoglobins and by making use of Perutz's atomic models of hemoglobin, we have found that NMR spectroscopy can provide detailed and in some cases unique information about the heme environment, functional properties of the alpha and Beta chains, and the nature of subunit interactions during the oxygenation process. We would like to continue and to expand our NMR studies of hemoglobins. BIBLIOGRAPHIC REFERENCES: C. Ho, L.W.M. Fung, K.J. Wiechelman, G. Pifat, and M.E. Johnson, "Recent NMR Studies on Quaternary Structural Transitions in Human Hemoglobins." Progr. Clin. Biol. Res. 1, 43 (1975). L.W.M. Fung, C. Ho, E.F. Roth, Jr., and R.L. Nagel, "The Alkylation of Hemoglobin S by Nitrogen Mustard: High-Resolution Proton Nuclear Magnetic Resonance Studies," J. Biol. Chem. 250, 4786 (1975).